1. Field of the Invention
The present invention relates to a process for preparing 14.alpha.-hydroxy-4-androstene-3,6,17-trione, and particularly to a process for preparing said compound easily and in high yield by oxidation caused by light.
2. Description of the Prior Art
Steroids show various physiological activities due to their tertial configurations. In particular, it is now evident that such physiological activities are greatly affected by whether oxygen atoms bound to the steroid skeleton are those of hydroxyl groups or those of double-bonded oxygens. Consequently, various methods for the oxidation of the hydroxyl groups bound to the steroid backbones and for reduction of carbonyl groups thereof have been investigated.
The present inventors previously found that 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione was produced by microbial transformation of steroid when 4-androstene-3,17-dione was added as a substrate to a culture medium for Acremonium strictum, and thus applied for a patent as Japanese Patent Application No. 24598/1987 since the compound has a strong aromatase inhibitory activity. Thereafter, as a result of intensive study on 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione, the present inventors confirmed that 14.alpha.-hydroxy-4-androstene-3,6,17-trione has a stronger aromatase inhibitory activity than 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione and that 14.alpha.-hydroxy-4-androstene-3,6,17-trione is useful as an antitumor agent, and then applied for a patent as Japanese Patent Application No. 24594/1987. These patent applications by the present inventors have been applied in an integrated form in U.S. Ser. No. 279,596 and in EP Appln. 88.901462.7.
14-.alpha.-hydroxy-4-androstene-3,6,17-trione is a compound having the following formula. ##STR1##
In order to obtain 14-.alpha.-hydroxy-4-androstene-3,6,17-trione, the hydroxyl group at the 6.beta. position of 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione is selectively oxidized as mentioned above using an oxidizing agent, wherein the use of activated manganese dioxide or chromic acid as the agent is required.
Steroid compounds in which an oxygen atom is bound to the carbon at position 6, not being limited to the compound above, have prominent physiological activities and hence various investigations have been conducted. However, most of the compounds have been obtained by oxidation with the use of metal catalysts or oxidizing agents such as activated manganese dioxide and chromic acid.
However, in the oxidation reaction using such oxidizing agents, in order to remove metal catalysts such as chromium or manganese and to remove excessive oxidizing agents remaining in the reaction system, complicated steps such as extraction of the solvents or fractionation using silica gel chromatography were required. Moreover, the recovery of the desired compound was not necessarily satisfactory.
Introduction of a hydroxyl group to position 6.beta. using excitation energy with the aid of light has been reported by R. Gandi et al. (Journal of Organic Chemistry 32, 2647-2649, 1967). However, a process for oxidizing a hydroxyl group at position 6.beta. of steroid compounds with the aid of light has not been reported and not yet known.